“Adding total body irradiation to preparative lymphodepletion chemotherapy prior to the adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) had no effect on tumor regression in patients with metastatic melanoma, according to the results of a study published in the Journal of Clinical Oncology.

“However, adoptive cell transfer of TILs did mediate the objective complete response of 24% of patients.

“ ‘The nonmyeloablative chemotherapy regimen thus seemed to provide sufficient lymphodepletion for successful adoptive transfer without the need to add total body irradiation,’ wrote researchers led by Stephanie L. Goff, MD, of the National Cancer Institute.”

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“The investigational cancer vaccine CRS-207 may improve response and survival when given with chemotherapy in patients with malignant pleural mesothelioma (MPM) according to results of a phase Ib trial.

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“After nearly 30 years of research, tumor-infiltrating lymphocyte (TIL) technology is being investigated as a means of producing personalized immunotherapy for patients with metastatic melanoma in a small clinical trial that may help open the door for broader application in other solid tumor types.

“The form of adoptive cell therapy, which utilizes TILs from the patient’s tumor, represents an intriguing way of overcoming the immunosuppressive power of cancer, according to Jeffrey S. Weber, MD, PhD. The melanoma expert provided an overview of the technology and its potential benefit in a lecture for oncologists and oncology professionals presented by Targeted Oncology, a division of MJH Associates, the publisher of OncologyLive, on February 19 in Miami Beach, Florida. Weber is the deputy director of the Laura and Isaac Perlmutter Cancer Center, co-director of its melanoma program, and head of Experimental Therapeutics at NYU Langone Medical Center.”

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“Tumor infiltrating lymphocyte (TIL) technology represents an intriguing way of overcoming the immunosuppressive power of cancer, according to Jeffrey S. Weber, MD, PhD.

“Weber provided an overview of the technology and discussed its potential benefit to oncologists and oncology professionals in a lecture presented by Targeted Oncology on February 19, 2016.

“ ‘It’s yet another way of inducing remissions of long duration using an immunotherapeutic approach that’s different than ipilimumab and different than nivolumab or pembrolizumab,’ said Weber, the deputy director of the Laura and Isaac Perlmutter Cancer Center, co-director of the Melanoma Program, and head of Experimental Therapeutics at NYU Langone Medical Center. ‘It’s got its own toxicity, but you can fail this therapy and respond to ipilimumab or respond to nivolumab or pembrolizumab. You can fail nivolumab or pembrolizumab or ipilimumab and respond to this—they’re not cross-reactive.’ “

“In dramatic contrast, 10-year estimates for RFS among 456 patients who received the same chemotherapy regimen followed by weekly paclitaxel plus trastuzumab followed by trastuzumab alone were virtually identical in patients with high- and low-levels of STILs at 80% and 80.1%, respectively (HR 1.26; 95% CI 0.50-3.17; P=0.63).”

“In an analysis of the NeoALTTO trial reported in JAMA Oncology, Salgado et al found that a higher level of tumor-infiltrating lymphocytes was associated with improved pathologic compete response rate and event-free survival independent of neoadjuvant treatment received in patients with HER2-positive early breast cancer.

“In NeoALTTO, 455 patients were randomly assigned to receive neoadjuvant trastuzumab (Herceptin), lapatinib (Tykerb), or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks and three cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. Percentage of tumor-infiltrating lymphocytes were measured by hematoxylin-eosin stained core biopsy sections taken at diagnosis.”

“High levels of tumor-infiltrating lymphocytes served as an independent positive predictive marker for EFS and pathological complete response in HER-2–positive early breast cancer treated with chemotherapy and anti-HER–2 agents, according a secondary analysis of the NeoALTTO trial.

“ ‘Increasingly, oncogenic addiction, in which tumors become dependent on a sole oncogenic pathway for growth, is thought to promote a tumor microenvironment conducive to immune escape,’ Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre at the University of Melbourne, and colleagues wrote. ‘Although this had not been shown yet for HER-2 oncogenic signaling, one could speculate that anti-HER–2 therapy may not only work in a cell-intrinsic manner but may also reserve HER-2–induced immunosuppression as a mechanism for action.’

“Lion Biotechnologies, Inc. (Nasdaq: LBIO), a biotechnology company that is developing novel cancer immunotherapies based on tumor infiltrating lymphocytes (TIL), today announced that researchers from Moffitt Cancer Center reported positive results from a pilot trial of TIL and ipilimumab in patients with metastatic melanoma. The data from the trial, which Lion partially sponsored, were presented at the Society of Surgical Oncology 2015 meeting in Houston, TX on Friday, March 27, 2015.

“The Phase 1 trial was conducted at Moffitt Cancer Center in 12 patients with metastatic melanoma, with the objective of determining the safety and feasibility of combining TIL therapy with the CTLA-4 checkpoint inhibitor, ipilimumab. Patients were treated with ipilimumab one week prior to tumor harvest for TIL expansion, a second time while their TIL were being expanded, and two more times following TIL transfer.

“Of the 12 patients enrolled in the trial, 11 went on to receive their autologous TIL, with five out of the 11 TIL-treated patients (46%) responding to treatment (one complete response and four partial responses), consistent with response rates from previous TIL studies in metastatic melanoma. Notably, the researchers observed that following a single infusion of ipilimumab, TIL grew to higher numbers than historically had been observed in previous studies, in which ipilimumab was not administered prior to tumor harvest. In addition, only one of the 12 enrolled patients (8%) was ineligible for TIL transfer, indicating relatively high patient adherence to trial protocol.

” ‘Ipilimumab has potential to enhance the effectiveness of TIL therapy by boosting the concentration of tumor-reactive T cells in the tumors of patients prior to TIL harvest, and by controlling disease before TIL transfer,’ said Sangeetha Prabhakaran, MD, the study’s presenting author. ‘Based on the results of this study, we conclude that TIL-ipilimumab combination treatment is both safe and feasible. Furthermore, this approach serves as a model for future efforts to combine TIL with PD-1/PD-L1 blockade and other emerging immune checkpoint inhibitors.’ “

Lately, immunotherapy—treatment that helps the body’s own immune system fight cancer—has made frequent appearances in news headlines. Indeed, researchers have reported remarkable clinical trial results for a new class of drugs known as ‘immune checkpoint blockade drugs‘ in the treatment of metastatic melanoma, lung, and kidney cancers. Approvals from the U.S. Food and Drug Administration (FDA) for the drugs Keytruda and Opdivo for melanoma and lung cancer have quickly followed. However, it may be that immunotherapies won’t work for all cancers, but only for those considered to be ‘immunogenic’; that is, cancers that trigger activation of the immune system. Researchers are studying different types of breast cancer to determine whether they are immunogenic, and what that might mean for their prognosis and treatments. Continue reading…